Phaidra - University of Veterinary Medicine Vienna
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Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice
No full textDespite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments-a nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore, we show that different molecular mechanisms converge on similar behavioural phenotypes by demonstrating that the autism models Cul3 and Ptchd1, despite having similar behavioural phenotypes, differ in their functional and molecular alteration. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment and define a nondevelopmental source of such deficits in ASD
JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression
No full textProstate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood.We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment.Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of Pten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1? production. Jun depletion in a Pten-deficient background prevented immune cell attraction which was accompanied by significant reduction of
active STAT3 and IL-1? and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1?, TNF-?, CCL3 and CCL8 in Pten-deficient prostates. Strikingly, JUN depletion reversed both the senescence-associated secretory phenotype and senescence-associated immune cell infiltration but had no impact on cell cycle arrest. As a result, JUN depletion in Pten-deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth.Our results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes
Feathered Lectures-Evidence of Perceptual Factors on Social Learning in Kea Parrots (Nestor notabilis)
No full textSocial learning describes the acquisition of knowledge through observation of other individuals, and it is fundamental for the development of culture and traditions within human groups. Although previous studies suggest that Kea (Nestor notabilis) benefit from social learning, experimental evidence has been inconclusive, as in a recent two-action task, all perceptual factors were ignored. The present study attempts to address this by investigating social learning in Kea with a focus on social enhancement processes. In an experiment with a captive group of Kea, we investigated whether individuals that had the opportunity to observe a conspecific performing a simple task subsequently show better performance in that task than a control group without prior demonstration. This study provides a strong tendency of greater success in skill acquisition in Kea as a result of social learning. Kea that observed a conspecific solving a task showed clear evidence of perceptual factors drawing attention to the relevant parts of the experimental apparatus and manipulated these significantly more (100% of trials) than control birds (77.8% of trials). Combined with a strong trend (p = 0.056) of the test subjects solving the task more than the control subjects, this shows conclusively that Kea, at least when required to solve a task, do attend to perceptual factors of a demonstrated action
Fine-scale genetic structure and phenotypic divergence of a passerine bird population inhabiting a continuous Mediterranean woodland
No full textGenetic differentiation between populations inhabiting ecologically different habitats might appear because of limited dispersal and gene flow, which may lead to patterns of phenotypic divergence and local adaptation. In this study, we use dispersal, genotypic (24 microsatellite loci) and phenotypic (body size and clutch size) data to analyse patterns of genetic structuring and phenotypic divergence in a blue tit (Cyanistes caeruleus) population inhabiting a continuous and heterogeneous woodland along a valley. The two slopes of the valley differ in their forest formations and environmental conditions. Findings showed that most blue tits reproduced within their natal slope. Accordingly, microsatellite analyses revealed that populations of blue tits established in the two slopes show subtle genetic differentiation. The two genetic populations diverged in clutch size, exceeding the level of differentiation expected based on genetic drift, hence suggesting divergent selection (or other processes promoting divergence) on this life-history trait. Our findings reveal that restricted dispersal and spatial heterogeneity may
lead to genetic differentiation among bird populations at a surprisingly small scale. In this respect, it is worth highlighting that such differentiation occurs for an organism with high dispersal capacity and within a continuous woodland. Moreover, we show that small-scale ecological differences, together with limited gene flow, can result in selection favouring different phenotypes even within the same continuum population
Stocking density at feeders and drinkers and temporal feed restriction affects dairy cows\u27 drinking behavior
No full textWater is an essential resource for dairy cows, and its consumption is closely linked to feed intake. Social competition can lead to changes in drinking behavior, especially for subordinate cows. We studied how changes in stocking density at the feeder (1 or 2 cows per feeder), and drinker (6 or 12 cows per drinker) and a temporal feed restriction (14- or 24-h access) affects drinking in 4 groups of 6 cows each, following a Latin square design. We recorded drinking behavior within each group of 6 focal cows, and 2 were identified as most dominant, 2 as most subordinate, and the 2 others as intermediate, based on success in agonistic interactions at the drinker. Cows drank less water when feed availability was restricted (on average 5.3 ± 3.4 [SE] L/d less; 4.5% average difference). Subordinate cows also spent less time drinking when overstocked (9.3 ± 6.7 min/d less; 24.3% difference). During treatments with more competition, cows were more likely to be observed drinking in the hours after the peak in drinking observed for the control treatment. A high level of competition among group-housed animals is considered a welfare problem and can lead to injuries and reduced production. Our findings provide evidence that feed restriction and higher stocking density of cows at the drinker and feeders changes the drinking behavior of cows, with subordinate animals experiencing more pronounced effects
Discovery of the Alternaria mycotoxins alterperylenol and altertoxin I as novel immunosuppressive and antiestrogenic compounds in vitro
No full textAlternaria mycotoxins may pose significant challenges to food safety and public health due to the wide spectrum of reported adverse effects. Despite this, critical information on the immunomodulatory and antiestrogenic properties of most of these contaminants is still lacking. The present study aimed to identify the mycotoxins responsible for the immunosuppressive and antiestrogenic effects of a complex extract of Alternaria mycotoxins (CE) obtained by growing an Alternaria alternata strain on rice. Through a toxicity-guided fractionation procedure involving the production of CE-fractions by supercritical fluid chromatography and mycotoxin quantification by LC-MS/MS, the mycotoxins alternariol (AOH), tenuazonic acid (TeA), altertoxin I (ATX-I), and alterperylenol (ALTP) were identified as potential toxicologically relevant constituents contributing to the in vitro effects exerted by the extract. The assessment of the immunomodulatory effects, performed by applying the NF-?B reporter gene assay in THP1-Lucia™ monocytes, revealed the scarce contribution of AOH to the effects exerted by the CE. TeA showed no effect on the NF-?B pathway up to 250 µM, whereas ATX-I and ALTP suppressed the LPS-mediated pathway activation at concentrations???1 µM. The evaluation of antiestrogenic effects, performed in Ishikawa cells by applying the alkaline phosphatase assay, revealed the ability of ALTP (??0.4 µM) and ATX-I (??2 µM) to suppress the estrogen-dependent expression of enzyme activity. Given the risk of detrimental impacts stemming from alterations in endocrine and systemic immune responses by the investigated mycotoxins, further studies are needed to elucidate their underlying mechanisms of action and comprehensively evaluate the health risks posed by these toxins
Influence of processing of seitan, tempeh, and firm regular tofu on protein and lipid oxidation and Maillard reaction products formation
No full textThe impact of production and cooking on protein oxidation, lipid oxidation and Maillard reaction products (MRPs) generation was evaluated for firm regular tofu, tempeh, and seitan, three plant-based alternatives to meat products. Tofu showed higher content of protein-bound carbonyls (25.5 ± 5.4 nmol/mg protein) indicating higher degree of protein oxidation, while seitan exhibited the lowest content of MRPs like N(6)-carboxymethyllysine, as revealed by LC-MS/MS. Through determination of the peroxide value and thiobarbituric acid reactive substances as well as analysis of volatile oxidation compounds by GC-MS, an overall higher lipid oxidation level was found in tofu. Likewise, a mean 92.2 % depletion of naturally occurring antioxidant tocopherol, assessed by HPLC-DAD, was observed in tofu. Furthermore, acrylamide was detected in tofu at 196.0 ± 15.4 ?g/kg after frying at 190 °C. This study, therefore, concluded that practices used in tempeh and seitan processing are promising strategies to limit oxidation and Maillard reactions in food
Effect of a Broiler-Specific Light Spectrum on Growth Performance and Adrenocortical Activity in Chickens: A Pilot Study on a Commercial Farm
No full textThis study evaluated the effect of a broiler-specific light spectrum on productive performance corticosterone (fCC) and androgen dehydroepiandrosterone (fDHEA) concentrations in feathers, and glucocorticoid (GCMs) and androgen (AMs) metabolites in droppings of broilers. Two groups of female Ross 308 broilers were reared under white LED (WL, n = 9000) and broiler-specific LED (BSL, n = 9000) lights. The body weight (BW) of 150 randomly selected animals/groups was measured weekly. Droppings and feathers were collected at the end of the cycle (29 days) from 20 animals/group. The BSL group showed higher final BW than WL (1407 ± 11 vs. 1341 ± 15 g, respectively; p< 0.001) and higher indices of uniformity (76.8% vs. 61.2% animals in the 10% around the mean, respectively; p< 0.001). No difference between groups was found in fCC and fDHEA concentrations or in the fCC-fDHEA, indicating similar long-term HPA axis activity during the cycle. A higher concentration of GCMs was found in the BSL group, indicating higher glucocorticoid secretion before sampling, with neither a difference in AMs nor in GCMs-AMs. Finally, there was a positive correlation between fCC and fDHEA and between GCMs and AMs (p< 0.01). Our findings suggest that the use of broiler-specific light improved the productivity performances of chickens without long-term consequences on HPA activation. However, the results of this pilot study in a commercial farm setting must be interpreted with caution and need confirmatio
Immunological memory in a teleost fish: common carp IgM+ B cells differentiate into memory and plasma cells
No full textFrom ancient cold-blooded fishes to mammals, all vertebrates are protected by adaptive immunity, and retain immunological memory. Although immunologists can demonstrate these phenomena in all fish, the responding cells remain elusive, without the tools to study them nor markers to define them. Fundamentally, we posited that it is longevity that defines a memory cell, like how it is antibody production that defines a plasma cell. We infected the common carp with Sphaerospora molnari, a cnidarian parasite which causes seasonal outbreaks to which no vaccine is available. B cells proliferated and expressed gene signatures of differentiation. Despite a half-year gap between EdU labeling and sampling, IgM+ B cells retained the thymidine analogue, suggesting that these are at least six-month-old resting memory cells stemming from proliferating precursors. Additionally, we identified a lymphoid organ-resident population of plasma cells by the exceptional levels of IgM they express. Thus, we demonstrate that a teleost fish produces the lymphocytes key to vaccination success and long-term disease protection, supporting the idea that immunological memory is observable and universal across vertebrates
